The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/2/483/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 3, February 1, 1999 483-491

Articles

The Murine Nonclassical Class I Major Histocompatibility Complex–like CD1.1 Molecule Protects Target Cells from Lymphokine-activated Killer Cell Cytolysis

Chew Shun Chang*, Laurent Brossay{ddagger}, Mitchell Kronenberg{ddagger}, and Kevin P. Kane*

From the * Department of Medical Microbiology and Immunology, Faculty of Medicine, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; and the {ddagger} La Jolla Institute for Allergy and Immunology, San Diego, California 92121

Classical class I major histocompatibility complex (MHC) molecules, as well as the nonclassical class I histocompatibility leukocyte antigen (HLA)-E molecule, can negatively regulate natural killer (NK) cell cytotoxicity through engagement of NK inhibitory receptors. We show that expression of murine (m)CD1.1, a nonpolymorphic nonclassical MHC class I–like molecule encoded outside the MHC, protects NK-sensitive RMA/S target cells from adherent lymphokine-activated killer cell (A-LAK) cytotoxicity. Passage of effector cells in recombinant interleukin (rIL)-2 enhanced protection by mCD1.1, suggesting an expansion of relevant A-LAK population(s) or modulation of A-LAK receptor expression. Murine CD1.1 conferred protection from lysis by rIL-2–activated spleen cells of recombination activating gene (Rag)-1–/– mice, which lack B and T cells, demonstrating that mCD1.1 can protect RMA/S cells from lysis by NK cells. An antibody specific for mCD1.1 partially restored A-LAK lysis of RMA/S.CD1.1 transfectants, indicating that cell surface mCD1.1 can confer protection from lysis; therefore, mCD1.1 possibly acts through interaction with an NK inhibitory receptor. CD1.1 is by far the most divergent class I molecule capable of regulating NK cell activity. Finally, mCD1.1 expression rendered RMA/S cells resistant to lysis by A-LAK of multiple mouse strains. The conserved structure of mCD1.1 and pattern of mCD1.1 resistance from A-LAK lysis suggest that mCD1.1 may be a ligand for a conserved NK inhibitory receptor.

Key Words: CD1 • lymphokine-activated killer cell • natural killer cells • lysis • resistance

Address correspondence to Kevin P. Kane, Department of Medical Microbiology and Immunology, 660 HMRC, University of Alberta, Edmonton, Alberta T6G 2S2, Canada. Phone: 403-492-4997; Fax: 403-492-9828; E-mail: kevin.kane{at}ualberta.ca

Abbreviations used: A-LAK, adherent lymphokine-activated killer cell; KIR, killer cell inhibitory receptor; m, murine; NA-LAK, nonadherent lymphokine-activated killer cell; NKT cells, natural T cells; NP, nucleoprotein; Rag, recombination activating gene; TAP, transporter of antigen presentation.


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